Comparative actions of monomethoxyamphetamines on the release and uptake of biogenic amines in brain tissue.

para-Methoxyamphetamine (PMA), a known hallucinogen, is the most potent compound among methoxyamphetamines in disrupting behavior in rats. PMA, unlike d-amphetamine (A), did not induce stereotyped behavior and was less effective than A in stimulation of locomotor d-amphetamine-like effects, but ortho-methoxyamphetamine (OMA) was devoid of any locomotor stimulation. To investigate the reasons for the different behavioral effects caused by PMA, meta-methoxyamphetamine (MMA), OMA and A, a comparison was made among these drugs on the release and uptake of 3H-5-hydroxytryptamine (3H-5-HT), 3H-norepinephrine (3H-NE) and 3H-dopamine (3H-DA) in tissue slices of cerebral cortex and corpus striatum of rat brain. The potencies for the increased release of 3H-5-HT were found to be PMA greater than MMA greater than or equal to A greater than OMA in cerebral cortex of 3H-NE in cortex, A greater than or equal to PMA = MMA greater than OMA, and of 3H-DA in corpus striatum, A greater than MMA greater than PMA greater than or equal to OMA. The potencies for inhibiting the uptake of 3H-5-HT in cerebral cortex and corpus striatum were found to be PMA greater than MMA greater than A greater than OMA and of 3H-NE in cortex A greater than PMA greater than or equal to MMA greater than OMA, and 3H-DA in corpus striatum A greater than MMA greater than PMA greater than OMA. d-PMA is equipotent to l-PMA in increasing the release of 3H-5-HT but is more potent than l-PMA in blocking the uptake of 3H-5-HT. The high potency of PMA on increasing the release and inhibiting the uptake of 5-HT suggests than 5-HT may be involved in the production of hallucinogenic effects of PMA.